Endoscopic and histologic characteristics of serrated lesions

In recent years , a second pathway for colonic carcinogenesis , distinct from the adenomatous pathway, has been explored. This is referred to as serrated pathway and includes three types of polyp,characterised by a serrated appearance of the crypts:hyperplastic polyps(HP),sessile serrated adenomas(SSA)or lesions,and traditional serrated adenomas.Each lesion has its own genetic,as well as macroscopic and microscopic morphological features.Because of their flat aspect,their detection is easier with chromoendoscopy(carmin indigo or narrow-band imaging).However,as we show in this review,the distinction between SSA and HP is quite difficult.It is now recommended to resect in one piece as it is possible the serrated polyps with a control in a delay depending on the presence or not of dysplasia.These different types of lesion are described in detail in the present review in general population,in polyposis and in inflammatory bowel diseases patients.This review highlights the need to improve characterization and understanding of this way of colorectal cancerogenesis.     

Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma

Sessile serrated adenoma/polyps(SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a Cp G island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to "interval cancers". If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their(semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.     

Serrated adenoma prevalence in inflammatory bowel disease surveillance colonoscopy,and characteristics revealed by chromoendoscopy and virtual chromoendoscopy

BACKGROUND:

Sessile or nonpolypoid neoplastic lesions, including sessile serrated adenomas (SSAs), are difficult to detect in patients with inflammatory bowel disease (IBD).

OBJECTIVES:

To assess the prevalence and endoscopic features of SSA in IBD patients undergoing surveillance colonoscopy using novel endoscopic techniques.

METHODS:

Histology results of biopsies from a cohort of 87 patients (47 men; median age 51.4 years; median duration of disease 16.9 years; ulcerative colitis [n=40], Crohn disease [n=43], ischemic colitis [n=4]) with longstanding colonic IBD undergoing surveillance colonoscopy were reviewed. Lesions of dysplasia (adenoma-like mass, or dysplasia-associated lesion or mass), SSAs, adenoma-like polyps, hyperplastic polyps and inflammatory polyps were identified. Surveillance colonoscopy using high-definition alone, or with iScan (Pentax, USA) dye-sprayed or virtual chromoendoscopy was performed. Lesion characteristics were described before histological diagnosis.

RESULTS:

Fourteen SSAs were detected in 87 (11%) IBD patients. The endoscopic characteristics of SSA lesions were: nonpolypoid appearance (86%), predominant localization in the proximal colon (79%), >6 mm in size (79%), cloudy cover (64%), Kudo pit pattern modified type IIO (86%) and irregular spiral vascular pattern (79%). Among the 44 SSAs and hyperplastic polyps found in the present study, the above characteristics of SSA at colonoscopy had a sensitivity of 92.86% (95% CI 66.06% to 98.8%) and specificity of 93.33% (95% CI 77.89% to 98.99%) in predicting a histological diagnosis of SSA (positive predictive value 86.67%, negative predictive value 96.55%).

CONCLUSION:

SSAs are a common finding at surveillance colonoscopy in IBD and have several characteristic features. Further studies are needed to evaluate the natural history of these lesions in IBD patients.     

A significant number of sessile serrated adenomas might not be accurately diagnosed in daily practice

Background/Aims

The diagnosis of hyperplastic polyps (HPs) may involve a conglomeration of subgroups of serrated polyps. The diagnosis of HPs may therefore be revisited if this is sessile serrated adenoma (SSA). The aim of this study was to determine clinically and endoscopically relevant information associated with reclassification to SSA.

Methods

After reviewing the data from 1,372 patients who underwent colonoscopic polypectomy, 49 HPs larger than 10 mm were analyzed in this study. Two gastrointestinal pathologists reclassified each of the original 49 HPs as conventional HPs, SSAs, and others.

Results

Among the 49 initially diagnosed HPs, 18.4% were reclassified into SSAs or mixed polyps. Overall architectural features were useful for the diagnosis of SSA, but cytological features were less useful. The patient and polyp characteristics did not differ between HPs with and without reclassification of the initial pathological diagnosis.

Conclusions

A significant number of SSAs might not be accurately diagnosed in daily clinical practice without any predilection for size, shape, and location. Therefore, when large HPs are diagnosed in clinical practice, it is necessary for physicians to have greater awareness of the diagnosis of SSA and to individualize subsequent surveillance.     

Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

Serrated polyps of the colon and rectum: Endoscopic features including image enhanced endoscopy

In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy(IEE). Histopathologically, lesions with serrated structures are typically classified into the following three types based: hyperplastic polyps(HPs), traditional serrated adenomas(TSAs), and sessile serrated adenoma/polyps(SSA/Ps). Both HP and SSA/P often present as dark-green colors on auto fluorescence imaging(AFI) colonoscopy that are similar to the normal surrounding mucosa. In contrast, TSAs often have elevated shapes and present as magenta colors that are similar to the tubular adenomas. The superficial type of TSA also includes many lesions that present as magenta colors. When SSA/Ps are associated with cytological dysplasia, many lesions present with magenta colors, whereas lesions that are not associated with cytological dysplasia present with dark-green colors. When observed via narrow band imaging(NBI), many SSA/P include lesions with strong mucous adhesions. Because these lesions are observed with reddish mucous adhesions, we refer to them as "red cap sign" and place such signs among the typical findings of SSA/P. Because the dilatation of the pit in SSA/P is observed as a round/oval black dot on magnified observations, we refer to this finding as Ⅱ-dilatation pit(Ⅱ-D pit) and also positioned it as a characteristic finding of SSA/P. In contrast, dilatations of the capillary vessels surrounding the glands, such as those that occur in tubular adenoma, are not considered to be useful for differentiating HPs from SSA/Ps. However, in cases in which SSA/P is associated with cytological dysplasia, the dilatation of capillary vessels is observed in the same area. When submucosal layer invasion occurs in the same area, the blood flow presents with irregularities that are similar to those of common colorectal cancer at an early stage and disappears as the invasion proceeds deeply. The surface pattern of invasive cancer that is observed at the tumor surface is also likely to disappear. Based on the above results, we considered that the differentiations between HP and TSA, between TSA and SSA/P, and between HP and SSA/P might become easier due to the concomitant use of white light observation and IEE. We also concluded that AFI and NBI can be useful modalities for SSA/P lesions associated with cytological dysplasia.     

Pathogenesis and Management of Serrated Polyps: Current Status and Future Directions

Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.     

Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps

AIM: To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS: Broad division of serrated lesions of the colorectum into hyperplastic polyps (HPs), traditional serrated adenomas (TSAs), and sessile serrated adenomas/polyps (SSA/Ps) has been proposed on the basis of recent molecular biological studies. However, few reports have examined the colonoscopic features of these divisions, including magnified colonoscopic findings. This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011. Patient characteristics (sex, age), conventional colonoscopic findings (location, size, morphology, color, mucin) and magnified colonoscopic findings (pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies, and were compared with histopathological diagnoses. The pit patterns were categorized according to Kudo’s classification, but a more detailed investigation was also performed using the subclassification [type II-Open (type II-O), type II-Long (type II-L), or type IV-Serrated (type IV-S)] proposed by Kimura T and Yamano H.RESULTS: Lesions comprised 23 HPs (23/118: 19.5%), 39 TSAs (39/118: 33.1%: with cancer in one case), 50 SSA/Ps (50/118: 42.4%: complicated with cancer in three cases), and six others (6/118: 5.1%). We excluded six others, including three regular adenomas, one hamartoma, one inflammatory polyp, and one juvenile polyp for further analysis. Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs (SSA/P vs HP, 13.62 ± 8.62 mm vs 7.74 ± 3.24 mm, P < 0.001; SSA/Ps vs TSA, 13.62 ± 8.62 mm vs 9.89 ± 5.73 mm, P < 0.01); common in the right side of the colon [HPs, 30.4% (7/23): TSAs, 20.5% (8/39): SSA/P, 84.0% (42/50), P < 0.001]; flat-elevated lesion [HPs, 30.4% (7/23): TSAs, 5.1% (2/39): SSA/Ps, 90.0% (45/50), P < 0.001]; normal-colored or pale imucosa [HPs, 34.8% (8/23): TSAs, 10.3% (4/39): SSA/Ps, 80% (40/50), P < 0.001]; and with large amounts of mucin [HPs, 21.7% (5/23): TSAs, 17.9% (7/39): SSA/Ps, 72.0% (36/50), P < 0.001]. In magnified colonoscopic findings, 17 lesions showed either type II pit pattern alone or partial type II pit pattern as the basic architecture, with 14 HPs (14/17, 70.0%) and 3 SSA/Ps. Magnified colonoscopy showed the type II-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7% (41/49), specificity 85.7% (54/63)]. Cancer was also present in three lesions, in all of which a type VI pit pattern was also present within the same lesion. There were four HPs and four TSAs each. The type IV-S pit pattern was characteristic of TSAs [sensitivity 96.7% (30/31), specificity 89.9% (72/81)]. Cancer was present in one lesion, in which a type VI pit pattern was also present within the same lesion. In our study, serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings. The pit pattern diagnosis using magnifying colonoscopy, particularly magnified colonoscopic findings using subclassifications of surface architecture, reflected the pathological characteristics of SSA/Ps and TSAs, and will be useful for colonoscopic diagnosis.CONCLUSION: We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy.     

Calcium and vitamin D in the serrated neoplastic pathway: Friends or foes?

Sessile serrated adenoma/polyps(known as SSA/Ps) may play an important role in the development of interval colorectal cancer(CRC). These lesions are more difficult to detect with conventional endoscopy and they may quickly turn into CRC, especially when dysplasia has developed. Therefore, primary or secondary chemoprevention may be an appealing strategy at a population level. Calcium and vitamin D have been shown in epidemiological studies to reduce the risk of CRC and conventional adenomas, but the evidence regarding their effect on SSA/Ps is controversial. In this editorial we comment on the results of a recent randomized controlled trial investigating the effect of calcium and vitamin D on the development of serrated lesions, summarizing the possible antineoplastic mechanisms of calcium and vitamin D, and discussing the differences found with previous observational reports.     

Sessile serrated adenoma/polyps: Where are we at in 2016?

It is currently known that colorectal cancers(CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway(50%-70%); the mutator "Lynch syndrome" route(3%-5%); and the serrated pathway(30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps(HP),sessile serrated adenomas/polyps(SSA/P) and traditional serrated adenomas(TSA),the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders,submucosal injection of a dye solution(for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions.     

Serrated polyps of the colon and rectum: Remove or not?

In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps(HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive rectosigmoid HPs are removed. However, in Asian countries, the treatment strategy for colorectal serrated polyps has remained unestablished. Therefore, in this review, we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions ≥ 6 mm in size, and traditional serrated adenomas of any size.     

Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: Current status and management

Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image‐enhanced endoscopic technique; and management of these lesions.     

结直肠锯齿状病变的癌变机制及内镜诊断研究进展

结直肠锯齿状病变以往被认为是一种良性病变,近10年的研究表明其具有恶性潜能,锯齿状途径被认为是除腺瘤—癌、炎症—异型增生—癌变、de novo癌途径外新的结直肠癌癌变途径。据最新的世界卫生组织分类标准,锯齿状病变分为增生性息肉、无蒂锯齿状病变和传统锯齿状腺瘤3种类型。由于锯齿状病变具有相对特异的癌变途径及内镜下特点,本...     

Anti-Ro/SSA antibodies are associated with severe mitral valve regurgitation in patients with systemic lupus erythematosus

Objective: To assess whether anti-Ro/SSA antibodies are associated with cardiac valve disease in lupus.

Methods: A single-center, medical chart review was performed. Lupus patients were divided according to its anti-Ro/SSA status and subgroups were compared for valvular abnormalities and other characteristics. Dependence of anti-Ro/SSA reactivity to anti-Ro52/TRIM21 antibodies was also evaluated.

Results: Eighty-nine lupus patients were analyzed. The most common valvular abnormalities were tricuspid (60%), mitral (41%) and pulmonary (14%) regurgitation. Thirty-six patients were positive and 53 negative for anti-Ro/SSA antibodies. In patients positive to anti-Ro/SSA, a difference was noted for anti-dsDNA (67 versus 45%; p?=?0.04) and anti-La/SSB (19 versus 2%; p?=?0.004) antibodies. An association between anti-Ro/SSA antibodies and severe mitral regurgitation was observed; indeed, 4/15 patients with anti-Ro/SSA and mitral regurgitation had severe forms of valvulopathy as compared to only 1/22 patients with mitral regurgitation but negative to such antibody (27 versus 5%; p?=?0.02). Anti-Ro/SSA antibodies significantly elevated the risk of severe mitral regurgitation (OR?=?5). Anti-Ro52/TRIM21 levels (103?±?29 versus 42?±?43?U/mL; p?=?0.03) and anti-Ro52/TRIM21:?anti-Ro/SSA ratios (0.88?±?0.02 versus 0.35?±?0.37; p?=?0.03) were higher in patients with mitral valve regurgitation than in those with no valvulopathy.

Conclusion: Anti-Ro/SSA antibodies, mainly against Ro52/TRIM21 antigens, may be pathologically involved in lupus-associated mitral valve regurgitation.     

结直肠无蒂型锯齿状腺瘤的临床病理特征

无蒂型锯齿状腺瘤（SSA）属结直肠锯齿状病变之一,具有独特的形态学特点、生物学行为和分子基因学改变,其内镜形态和组织学特征有别于其他结直肠锯齿状病变,且与新近提出的结直肠癌变的锯齿状通路密切相关.近年研究发现SSA是微卫星不稳定性癌的前期病变,可直接发生癌变.但目前国内尚缺乏对这一病变的认识.本文就SSA的定义、形态学特征和病理组织学诊断标准作一综述,旨在提高临床医师对这一病变的认识.     

Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs

INTRODUCTION: Invasive GH-secreting pituitary adenomas are rarely cured by surgery and although long-term therapy with somatostatin analogs (SSAs) may be employed, hormonal control is achieved in only 60% of cases. The impact of tumor debulking on subsequent control of acromegaly with SSAs has not been studied previously. METHODS: We studied retrospectively the response to SSA therapy in acromegalic patients before and after incomplete surgical tumor excision. A case review identified 24 acromegalic patients who had received SSA therapy for > or = 1 month before and after gross total resection or debulking of adenomas. No patient received radiotherapy or combination treatment with SSAs and dopamine agonists during the study. GH and IGV-I responses to SSAs were recorded pre- and postoperatively. Postoperative SSA therapy was begun after a washout period of 1-3 months to assess the hormonal effects of the surgery alone. RESULTS: Before preoperative SSA treatment, 24/24 (100%) patients had elevated GH levels and IGF-I levels were elevated in 19/21 (90.5%) patients with recorded values. During preoperative SSA treatment, GH and IGF-I levels were normalized in 7/24 (29.2%) and 11/24 (45.8%) patients respectively. Following postoperative washout, GH was controlled in only 3/24 (12.5%) patients, while IGF-I was controlled in 8/19 (42.1%) patients with available data. During the second SSA treatment period, normal GH levels were seen in 13/24 (54.2%) patients, while IGF-I control was noted in 18/23 (78.3%). CONCLUSION: Gross total tumor resection or debulking increases the likelihood of achieving biochemical disease control with SSAs in acromegalic patients with adenomas that were not amenable to complete surgical resection and in whom primary SSA therapy was unable to achieve good biochemical control.     

Association of anti-Ro/SSA antibody with response to biologics in patients with rheumatoid arthritis

Objective: To compare the effectiveness of three different biologics in anti-Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA).

Methods: The study subjects were 110 biologics naïve patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody-negative patients.

Results: We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-β levels.

Conclusions: Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-β levels, but not to TCZ and ABT.     

Clinical and laboratory features of anticentromere antibody positive primary Sj?gren's syndrome.

OBJECTIVE: To determine whether the clinical and laboratory characteristics of anticentromere antibody (ACA) positive, anti-SSA/Ro antibody (SSA) negative primary Sjogren's syndrome (SS) differ from SSA positive, ACA negative primary SS. METHODS: Twelve patients with ACA positive primary SS (ACA SS) and 19 patients with SSA positive primary SS (SSA SS) were examined. We compared the age, laboratory data, proportion with Raynaud's phenomenon (RP), activity of natural killer cells (NK), titer of antibodies against Epstein-Barr virus, and histological findings of minor labial salivary glands. The presence of anti-chromo antibodies (AChA) was evaluated by immunoblotting of patients' sera. RESULTS: The mean age of the ACA SS group was higher than that of the SSA SS group (p < 0.05). Serum IgG level was lower in ACA SS than in SSA SS (p < 0.0001). Serum IgG level of the ACA SS group with one exception was close to the normal range. Leukocytopenia was less frequently observed in ACA SS than in SSA SS (p < 0.05). RP was seen more frequently in the ACA SS group than the SSA SS group (p < 0.05). NK activity of the ACA SS group was higher than that of the SSA SS group (p < 0.05). Most of the ACA SS patients' NK activity was normal, in contrast to the tendency for NK activity in SS to be low. Virus capsid antigen IgA titer of the ACA SS group was lower than that of the SSA SS group (p < 0.05). Histological findings of minor labial salivary glands of both groups showed a similar severity of lymphocytic infiltrates, destruction of normal structures, and pattern of infiltrating lymphocyte subsets. AChA was positive in 11 of the 12 sera of ACA SS patients. CONCLUSION: The results confirm that ACA positive primary SS differs from SSA positive classic SS in several significant respects.     

Differential expression of Ro/SSA 60 kDa and La/SSB, but not Ro/SSA 52 kDa, mRNA and protein in minor salivary glands from patients with primary Sjögren's syndrome

OBJECTIVE: To analyze the protein and messenger RNA (mRNA) expression of La/SSB, Ro/SSA 60, and Ro/SSA 52 antigens in minor salivary glands (MSG) from patients with primary Sj?gren's syndrome (pSS). METHODS: La/SSB, Ro/SSA 60, and Ro/SSA 52 protein expression was studied by immunohistochemistry in MSG from 26 patients with pSS and 16 controls. mRNA expression was determined by real-time polymerase chain reaction in MSG of 10 patients with pSS and 7 controls. RESULTS: La/SSB and Ro/SSA 60, but not Ro/SSA 52, mRNA expression was higher in samples from patients with pSS compared to controls (p < 0.05). La/SSB protein had higher expression in the cytoplasm of ductal cells than in the cytoplasm of mucous acinar cells in patients with pSS (p = 0.013) but not in controls. Ro/SSA 60 had higher expression in the cytoplasm of ductal cells than in the cytoplasm of serous acinar cells in patients with pSS (p = 0.006) but not in controls. The Ro/SSA 52 expression pattern was similar in patients and controls. There was no association between circulating autoantibodies to Ro/SSA or La/SSB and the aberrant expression of the cognate autoantigens. CONCLUSION: The increased Ro/SSA 60 and La/SSB mRNA expression in MSG of patients with pSS as well as the differential Ro/SSA 60 and La/SSB protein expression in ductal cells of MSG in patients with pSS suggest that these these 2 autoantigens, but not Ro/SSA 52, are probably involved in triggering and maintaining the tissue-specific autoimmune response in pSS MSG and may contribute to the antigen-driven immune response and local autoantibody production in pSS.